Un ampio studio di revisione, pubblicato sulla rivista scientifica Molecular Psychiatry (gruppo Nature), ridimensiona il collegamento tra serotonina e depressione. Anche le terapie andranno riorientate se la depressione non è strettamente causata della serotonina?
The theory that interprets the cause of depression as a biochemical imbalance in the brain and, mainly, as a deficiency of the neurotransmitter serotonin, has been under scrutiny for years. In fact, a significant part of the international community of psychiatrists believes that this hypothesis (which predominates) has never been convincingly proved. On the contrary, this would also explain why, in spite of worldwide success over at least three decades, the most commonly used antidepressant drugs today (all based on serotonin) sometimes prove ineffective.
Now a major review of studies on the subject, called an umbrella review (a review that not only brings together studies, but also identifies links between the findings of previous reviews and/or meta-analyses), offers new arguments for the sceptics. This extensive 'reinterpretation', published in the Nature group's scientific journal Molecular Psychiatry, was carried out by an international team coordinated by University College London: in particular, by two experts in the field, Joanna Moncrieff, co-director of the Critical Psychiatry Network (a group working together with the Council for Evidence-based Psychiatry), and Mark Horowitz, a member of the International Institute of Psychiatric Drug Withdrawal (IIPDW).
To reach their conclusions, the psychiatrists examined hundreds of studies, involving tens of thousands of patients, divided into six categories, as the issue of the biochemistry of depression can be approached from many different perspectives.
Causes of depression and drugs: surprising results
To begin with, although it is true that drugs do increase serotonin levels (in various ways), this does not necessarily imply that the increase combats depression. Researchers argue that almost all drugs have an emotionally numbing effect, and this may give patients the impression of feeling less depressed.
One of the areas of research focused, in particular, on the different concentrations of serotonin and its circulating metabolites in the blood and brain in patients who are on medication and those who are not. Researchers say that it cannot be quantified and this is important, because for a long time the focus was precisely on increasing serotonin circulation.
Another topic was serotonin receptors, i.e. proteins, located on the surface of nerve cells, that 'sense' its presence and transform this into biological actions. Again, at least for the various subtypes of receptors that have always been indicated as being responsible there seems to be no difference – according to researchers - between those who take the drugs and those who do not, and, indeed, sometimes the opposite is seen. Serotonin receptor activity would, in short, increase in the depressed, and not vice versa (although the data on this was not always clear).
Similar findings apply to serotonin transporters – SSRIs - the proteins on the surface of nerve cells that, like revolving doors, admit the neurotransmitter to the cell.
Some studies then explored the involvement of serotonin indirectly, i.e. by artificially lowering its levels to see if this induced depression: this was not the case.
Extensive research into thousands of patients and people without depression also looked at the possible genetic basis for depression. The focus was mainly on the status of the gene that 'manages' serotonin transporters, but no differences emerged between depressives and non-depressives.
Finally, some research on people who regularly took antidepressants showed lowered serotonin, not increased serotonin as expected.
How come? According to researchers, the increase in serotonin produced by some antidepressants in the short term can lead to compensatory changes in the brain, which produce the opposite effect in the long term.
Is the serotonin level really a cause of depression?
All of these results led the University College researchers to conclude that “there is no support for the theory that depression is caused by reduced serotonin activity or concentration”.
Experts emphasise that this should not lead anyone to abruptly stop current treatment.
Doctors, however, should prescribe antidepressants more carefully and explain the issue in more depth to patients, while also exploring other avenues. For example, focusing on dealing with stressful or traumatic events in people's lives, addressing underlying factors such as poverty and loneliness, and using psychotherapy more extensively, along with other practices such as mindfulness.
For its part, research should continue conclude the University College scholars, to better clarify what happens in depression from a biochemical point of view, and to see how pharmacological treatment is useful. The phenomena underlying depression are probably much more complex than those recorded so far and, as a result, even pharmacological treatment will have to take into account unknown factors yet to be explored if they are to be effective.
